The majority of immunoglobulin in tears is of the immunoglobulin A (IgA) isotype, which is produced mainly by plasma cells of the lacrimal gland. The mechanism responsible for the lodging of IgA cells in this gland is unknown and probably not dependent on direct glandular encounter with antigen. Previous experiments have suggested that a TH cell from the lacrimal gland can influence certain B cells to differentiate into IgA plasma cells. The proposed investigations will examine purified T cell preparations from the lacrimal gland and attempt to better define their capabilities in inducing IgA B cell differentiation. These T cells will be further defined after preparing clones of the cells responsible for the IgA B cell differentiation. In a second series of experiments, mechanisms responsible for the T cell accumulation in the lacrimal gland will be investigated. Experiments will examine the physical attachments of T cell to lacrimal gland epithelial cells and other experiments will examine T cell migration inhibition by lacrimal gland tissue supernatants. Finally experiments will examine a role for the nervous system and some of its factors, neuropeptides, in affecting lacrimal gland, especially their role in altering lymphocyte populations. These proposed studies will attempt to explain the predominance of IgA producing cells along mucosal surfaces, specifically the lacrimal gland, with a long term goal of altering the numbers of such antibody producing cells. The studies not only examine important immune mechanisms involving T cell - B cell interactions, but examine the effects of the nervous system on immunological and cell biological mechanisms in the lacrimal gland. These studies will allow for a better understanding of lacrimal gland and other mucosal tissue function, and may eventually lead to methods for altering the function in response to infectious or autoimmune diseases of the external eye or other mucosal surfaces.